New Study Brings Hope For Reversal of Some Forms of Memory Loss

A new study has concluded that a type of age-related memory loss not related to Alzheimer’s disease could be reversible. A team of Columbia University Medical Center (CUMC) researchers, led by Nobel laureate Eric R. Kandel, MD, has concluded that deficiency in the hippocampus of the protein RbAp48 is likely a significant contributor to age-related memory loss. The great news is that this form of memory loss can be reversed.

For the study, Kandel’s team used postmortem human brain cells as well as mice. The conclusion of the study offers the strongest causal evidence to date that age-related memory loss and Alzheimer's disease are distinct conditions. The findings were published in the August 29, 2013 online edition of Science Translational Medicine.

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The study focus was to look for direct evidence that age-related memory loss is a separate disease from Alzheimer’s disease. The researchers performed gene expression analyses of postmortem brain cells from the dentate gyrus (DG) of eight people, ages 33 to 88, who were free of any brain disease. They used cells from the same people but from a different area of the brain for their controls. The DG is a subregion of the hippocampus that receives direct input from the entorhinal cortex (EC). The EC is a brain region that provides the major input pathways to the hippocampus and is unaffected by aging.

The analyses identified 17 possible genes that could be related to aging in the DG. The researchers found that the most significant changes occurred in RbAp48 whose expression declined steadily with aging across the study subjects.

Co-senior author Scott A. Small, MD, of the Alzheimer's Research Center at CUMC, was quoted as saying, “Until now… no one has been able to identify specific molecular defects involved in age-related memory loss in humans."

Mouse studies were used to determine whether RbAp48 plays an active role in age-related memory loss. These studies did prove that there was a reduction of RbAp48 protein in the DG of the mouse brains.

The researchers genetically inhibited RbAp48 in the brains of the healthy young mice. When doing so, they found the same memory loss as in aged mice. The exciting part is that when RbAp48 inhibition was turned off, the mice's memory returned to normal. In other words, the memory loss is reversible. "We were astonished that not only did this improve the mice's performance on the memory tests, but their performance was comparable to that of young mice," one researcher said.

Whether this finding will translate to humans is still unknown. But the researchers feel “the broader point is that to develop effective interventions, you first have to find the right target. Now we have a good target, and with the mouse we've developed, we have a way to screen therapies that might be effective, be they pharmaceuticals, nutriceuticals or physical and cognitive exercises."

The research team was encouraged by the fact that they were able to reverse age-related memory loss in mice. They concluded that, at the very least, “it shows that this protein is a major factor, and it speaks to the fact that age-related memory loss is due to a functional change in neurons of some sort.”

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There are many reversible brain conditions that can mimic Alzheimer’s disease. This is why it’s important to see a specialist when seeking a diagnosis. A year ago, the Wall Street Journal published online a story about many cases of false diagnoses. The story focused on medications that can cause symptoms similar to Alzheimer’s disease. According the article, “More than 100 other conditions, from vitamin and hormone deficiencies to rare brain disorders, can mimic Alzheimer's disease… Some are readily treatable.”

As with so much breaking news in research, more studies will be needed to replicate the findings of this CUMC study. Scientists will need to determine if the same approach will work with humans, reversing the memory loss many seniors suffer. Funding important research of this type should eventually provide doctors with the tools to more easily distinguish Alzheimer’s disease from other memory loss issues that, with proper treatment, could be reversible.